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蛋白质和肽经鼻给药在神经退行性疾病治疗中的应用

Intranasal Delivery of Proteins and Peptides in the Treatment of Neurodegenerative Diseases.

作者信息

Meredith M Elizabeth, Salameh Therese S, Banks William A

机构信息

Department of Pathology, University of Washington, Seattle, Washington, USA.

出版信息

AAPS J. 2015 Jul;17(4):780-7. doi: 10.1208/s12248-015-9719-7. Epub 2015 Mar 24.

Abstract

The blood-brain barrier (BBB) is a major impediment to the therapeutic delivery of peptides and proteins to the brain. Intranasal delivery often provides a non-invasive means to bypass the BBB. Advantages of using intranasal delivery include minimizing exposure to peripheral organs and tissues, thus reducing systemic side effects. It also allows substances that typically have rapid degradation in the blood time to exert their effect. Intranasal delivery provides the ability to target proteins and peptides to specific regions of the brain when administered with substrates like cyclodextrins. In this review, we examined the use of intranasal delivery of various proteins and peptides that have implications in the treatment of neurodegenerative diseases, focusing especially on albumin, exendin/GLP-1, GALP, insulin, leptin, and PACAP. We have described their rationale for use, distribution in the brain after intranasal injection, how intranasal administration differed from other modes of delivery, and their use in clinical trials, if applicable. Intranasal delivery of drugs, peptides, and other proteins could be very useful in the future for the prevention or treatment of brain related diseases.

摘要

血脑屏障(BBB)是阻碍肽和蛋白质向脑内进行治疗性递送的主要障碍。鼻内给药通常提供了一种绕过血脑屏障的非侵入性方法。使用鼻内给药的优点包括将对外周器官和组织的暴露降至最低,从而减少全身副作用。它还能使通常在血液中快速降解的物质有时间发挥其作用。当与环糊精等底物一起给药时,鼻内给药能够将蛋白质和肽靶向脑内的特定区域。在本综述中,我们研究了鼻内递送各种对神经退行性疾病治疗有意义的蛋白质和肽的应用,特别关注白蛋白、艾塞那肽/胰高血糖素样肽-1(GLP-1)、甘丙肽(GALP)、胰岛素、瘦素和垂体腺苷酸环化酶激活肽(PACAP)。我们描述了它们的使用原理、鼻内注射后在脑内的分布、鼻内给药与其他给药方式的差异,以及在适用情况下它们在临床试验中的应用。药物、肽和其他蛋白质的鼻内给药在未来预防或治疗脑部相关疾病方面可能非常有用。

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